Novo Nordisk prepares to swallow its rivals for breakfast

Novo Nordisk’s newest diabetes medicine needed to impress in phase III – and a first look at the data make for encouraging reading. Oral semaglutide is the most advanced GLP-1 agonist in pill form, and top-line results suggest that both efficacy and safety have held up versus injected rivals.

This will come as a relief to Novo, which is facing stiff competition in diabetes as well as increasingly muscular payers. Still, the Pioneer 1 study is only the first of 10 to report from a huge pivotal programme, and head-to-head trials versus rivals, due in the coming weeks, are arguably a more important test of the new pill (see tables below).

Hitting the primary endpoint in Pioneer 1, which was a placebo-controlled study, is an important win from a regulatory standpoint. But this is only the first step in oral semaglutide’s journey. Next to report will be trials pitting oral sema against Boehringer Ingelheim and Lilly’s SGLT2 inhibitor Jardiance and Merck & Co’s DPP-IV inhibitor Januvia – both of which are pills – and its own once-daily injectable GLP-1 agonist, Victoza.

The table below details today’s results against other therapies, and oral sema stacks up very well on efficacy. Tolerability was also encouraging – Novo said rates of nausea ranged from 5% to 16%, which compares favourably with injectable products. Victoza and Ozempic, for example, have been associated with rates of around 28% and 20% respectively.

Novo has long dominated the GLP-1 space with once-daily Victoza; Ozempic, the once-weekly injected version of semaglutide, is also expected to become a hit. Consensus has sales of Ozempic, which was launched in the US this month, soaring to $3.8bn by 2022, according to EvaluatePharma.

Lilly’s once-weekly injectable GLP-1, Trulicity, has already proven a huge success since its launch in late 2014 – sales are seen reaching $4.1bn by 2022. So, while Ozempic represents a hugely important launch for Novo in terms of catching up with Lilly on its GLP-1 offerings, oral sema provides the clear blue water.

But oral sema will not only be competing with the injected GLP-1s - it brings the SGLT2s and the DPP-IVs into the picture. With many patients opting to try a pill before an injected therapy, oral sema also holds the potential to pull the GLP-1 class into earlier consideration.

Hence the importance of the upcoming side-by-side Pioneer trials which, while representing a huge risk, Novo in reality had no choice but to run. Diabetes drugs represent a huge cost to healthcare systems, and payers will be looking for reasons not to reimburse expensive, novel therapies.

Reason to worry?

Still, analysts are already pretty optimistic on oral sema – sales forecasts for 2022 stand at $889m, on the basis of a late 2020 launch.

But success depends not only on pending data; patients must also be willing to accept fairly strict administration rules. Lilly and analysts have described a dosing schedule that involves taking oral sema after at least six hours of fasting – so it would typically be taken before breakfast – with up to 100ml of water, followed by another half an hour of fasting, to ensure suffient systemic exposure of the active ingredient. Meanwhile, Novo maintains guidance will simply state “take 30 minutes before breakfast”.

Lilly, with much to lose here, has made much of this convenience aspect, and claims that compliance in the real world could harm effectiveness and put patients off.

In some cases this could certainly prove true, but comparative effectiveness and tolerabilty are surely more important. If oral sema proves itself a worthy competitor on these measures, Lilly really will have something to worry about.

Oral semaglutide phase III trials

Study

Setting

Enrolment

Data due

Trial ID

Pioneer 1

Vs placebo

703

Reported

NCT02906930

Pioneer 2

Vs Jardiance

816

Q2

NCT02863328

Pioneer 3

Vs Januvia

1,860

Q2

NCT02607865

Pioneer 4

Vs Victoza

690

Q2

NCT02863419

Pioneer 5

Vs placebo; moderate renal impairment

324

Q3

NCT02827708

Pioneer 6

CV outcomes

3,176

Q4

NCT02692716

Pioneer 7

Flexible dose adjustment vs Januvia

500

Q2

NCT02849080

Pioneer 8

Vs placebo in insulin-treated patients

720

Q4

NCT03021187

Pioneer 9

Vs placebo or Victoza; Japanese patients

240

Q4

NCT03018028

Pioneer 10

Vs Trulicity, combination study in Japanese patients

455

Q3

NCT03015220

This story has been updated with dosing information for oral semaglutide and new timelines for the Pioneer trial readouts.